Mutations

APP T714A (Iranian)

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.275332A>G
Genomic Mutation Name (NT1): g.284028A>G
dbSNP ID: rs63750643
Coding/Non-Coding: Coding
Genomic Region: Exon 17
Mutation Type: Point, Missense
Codon Change: ACA to GCA

Findings

This mutation was first reported in a three-generation Iranian pedigree with nine documented affected individuals and an average age of onset of approximately 55 years. The common feature of all the affected members of this family was progressive dementia consistent with AD, although motor apraxia was also observed in some cases. The reporting authors noted that the age at onset in this family was considerably older than the age reported for APP T714I, presumably because alanine causes less disruption to the transmembrane structure than isoleucine (Pasalar et al., 2002).

This mutation has been found in two additional studies. The mutation was detected in a Polish individual with Alzheimer's disease. In this patient, onset was at 44 years and the disease progressed rapidly, leading to severe memory impairment and other cognitive and behavioral deficits within four years (Zekanowski et al., 2003). A different clinical picture was associated with this mutation in another unrelated individual who was diagnosed with AD following a long prodromal phase (eight years of isolated amnesia). The clinical presentation in this individual was atypical in that it was also characterized by autonomic failure and seizures (Lindquist et al., 2008).

Neuropathology

The neuropathology associated with this mutation is not well characterized, but neuroimaging in one patient showed progressive cortical atrophy and white matter lesions (Lindquist et al., 2008).

Biological Effect

Unknown.

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References

Paper Citations

  1. . An Iranian family with Alzheimer's disease caused by a novel APP mutation (Thr714Ala). Neurology. 2002 May 28;58(10):1574-5. PubMed.
  2. . Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland. Exp Neurol. 2003 Dec;184(2):991-6. PubMed.
  3. . Atypical early-onset Alzheimer's disease caused by the Iranian APP mutation. J Neurol Sci. 2008 May 15;268(1-2):124-30. PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . An Iranian family with Alzheimer's disease caused by a novel APP mutation (Thr714Ala). Neurology. 2002 May 28;58(10):1574-5. PubMed.

Other mutations at this position

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